反应详情

A solution of NaOH (0.96 g, 22.68 mmol; assay=94.52%), water (22 ml), ethanol (22 ml, technical grade, contains ˜5% 2-propanol) and Trandolapril (4.5 g, 10.42 mmol; assay=99.7%) was stirred at an internal temperature ranging from about 20° C. to about 25° C. for 19 hours. After an in process control showed an almost complete saponification (by HPLC), the clear solution was acidified at a temperature ranging from about 20° C. to about 25° C. with 2N aqueous hydrochloric acid to a pH of 3.8 (22.8 mmol; the solution was seeded during acidification and the crystallization started at pH=4.6). The suspension was stirred at a temperature ranging from about 20° C. to about 25° C. (the stirring time in this case after pH adjustment was 47 hours and the pH was adjusted from 3.71 to 3.82 by an addition of 1 drop of 2N aqueous NaOH solution; generally a maximum stirring time of 5 to 6 hours at this pH is sufficient) and then filtered off. The wet product was washed with water (30 ml) and dried in vacuo (1-5 mbar) for 15 hours at 40° C. to give Trandolaprilat (yield: 4.0 g, 9.06 mmol, 86.9%; assay=91.15%; water content: 1.02-1.12%, ethanol content: 7.52-8.44%, 2-propanol content: 0.26-0.29, chloride content=not detected).

1. customthe crystallization
2. customranging from about 20° C. to about 25° C.
3. waitwas 47 hours
4. additionthe pH was adjusted from 3.71 to 3.82 by an addition of 1 drop of 2N aqueous NaOH solution
5. customa maximum stirring time of 5 to 6 hours
6. filtrationthen filtered off
7. washThe wet product was washed with water (30 ml)
8. customdried in vacuo (1-5 mbar) for 15 hours at 40° C.